French Response to Ebola : Research in a crisis situation
March 10, 2015
French Response to Ebola : Research in a crisis situation Pr JF - - PowerPoint PPT Presentation
French Response to Ebola : Research in a crisis situation Pr JF Delfraissy On behalf of the Task Force Interministrielle de la lutte contre Ebola March 10, 2015 Filovirus: classification Filovirus Genre: Ebolavirus Genre:
March 10, 2015
Filovirus Genre: Ebolavirus Genre: Marburgvirus 1 Espèce: Marburg marburgvirus
5 Espèces: Zaire ebolavirus Sudan ebolabirus Côte d’Ivoire ebolavirus Bundibugyo ebolavirus Reston ebolavirus
10/03/2015
(eau de javel et ses dérivés et solutions hydro alcooliques) à condition de respecter le temps de contact
GP=Glycoprotéine transmembranaire NP=Nucléoprotéine nécessaire à l’assemblage de la Capside VP24= inhibiteur antiviral VP35= inhibe la production d’IFN VP30=Transcription anti-terminator VP40= nécessaire pour assemblage et bourgeonnement de la capside L-Viral RNA Polymerase
Virus variability, impact on MAbs treatments, on diagnostic tests, clinical presentation, …
R0: nombre moyen de nouveaux cas générés par personnes malades Ebola (2) SARS (4) Grippe (3) Rougeole (18) Rubéole (10) Plus contagieux
Introduction dans la population humaine par contact étroit avec les fluides biologiques d’animaux infectés
Ebola Ebola
“In memoriam: Tragically, five co-authors, who contributed greatly to public health and research efforts in Sierra Leone, contracted EVD in the course of their work and lost their battle with the disease before this manuscript could be published. We wish to honor their memory.”
April 2014
14
− Ebola virus/H.sapiens-wt/GIN/2014/Makona Rivière Makona
(Kuhn JH, Andersen KG, Baize S et al. Viruses 2014;6:4760-99)
10/03/2015
– méconnaissance de la maladie dans la population – d’où retard aux mesures de contrôle de l ’épidémie
10/03/2015
ZEBOV : souche Zaïre Ebolavirus , SUDV : souche Sudan Ebolavirus, BDBV : souche Bundibugyo virus
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 ZEBOV SUDV BDBV 17
Létalité
Le Mali a éliminé officiellement Ebola (« Ebola free ») depuis le 18 janvier
18
19
67 74 76 78 80 88 92 94 97 106 121 126 139 148 154 159 162 162 164 35 37 40 41 43 46 51 55 56 59 62 72 81 87 90 94 100 101 101 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 20 40 60 80 100 120 140 160 180 S39 S40 S41 S42 S43 S44 S45 S46 S47 S48 S49 S50 S51 S52 S01 S02 S03 S04 S05 Cas confirmés Décès confirmés et probables Létalité (%)
Nombre de cas et de décès Létalité
Research Pr Yves Levy, CEO of Inserm, President of AVIESAN Diplomacy Mrs Christine Fages, Diplomat Health Pr Thierry Debord, Professor of Medicine Interior/Security
National Coordinator Pr Jean François Delfraissy, Under the authority of the Prime Minister
Administrative Chief Officer : Anne-Claire Amprou
development)
Health Alliance International
Cross
mid-December); FRC – French Red Cross
Alliance for International Medical Action
23
Essai Inserm
24
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
GUINEA
EBOLA RESPONSE IN WEST AFRICA INTERNATIONAL ORGANIZATIONS MEDICAL EVACUATION
Technical Assistance
French Experts embedded in UNMEER Financing extra support to WHO Medical evacuation within Guinea MEDEVAC coordination through EU Mechanism Emergency transport and hospitalization in France
WEST AFRICA
More than
MILLIONS Euros More than
MILLIONS Euros More than
MILLIONS Euros
ETUs
Macenta (50 beds) Beyla (20-30 beds) Kérouané (30-50 beds) Forecariah (20 beds) N’zérékoré (40 beds) Financing by French Gov 150 French HCW & 800 Guinean
Conakry Medical Unit Supply PPE and medical assets Supply extra food aid Strengthen basic health services Strengthen labs in 7 countries in West AFRICA Financing of prevention plans EBOLA outbreak (Mali , Cameroun & Ivory Coast)
France & Guinea 7days, 50 instructors for each 200 trainees/month First course Nov 15th
Training Center
20 beds 30 French HCW & 50 Guinean Estimate Opening Dec
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
IN A PUBLIC HEALTH CRISIS
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
Global program responsibility : Y. Levy (Pdt Aviesan)
Animation and scientific watch: Y. Yazdanpanah (IMMI) - REACTing
publications)
Operational management of projects
project
(budget, legal, human resources ...)
Scientific Committee Evaluation Scientific monitoring of projects
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
Emergence of Zaire Ebola Virus Disease in Guinea-Preliminary Report Baize S et al, N Engl J Med. 2014 Apr 16.
teams involved and of on-going research projects
20 October, 18 November Research priorities: Diagnostic, Treatment, Vaccination, clinical research, Social and Human sciences Funding: seed money from Aviesan and additional funding
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
Standardisation of a secure qualitative and quantitative molecular diagnosis protocol for filovirus infections; University Aix-Marseille; Institut Pasteur; CIRMF-Gabon
Identification of molecules that could inhibit EBOV replication and be rapidly transfered to clinic; Enyo-Pharma; Inserm
Efficacy of favipiravir in humans; Inserm; Ministry of Health Guinea; Institut Pasteur
Ebola Epidemic and social production of trust in Senegal; IRD; CNRS; UCAD and Ministry of Health, Senegal Rumors, disputes and controversies: perspectives from the digital world; IRD; McGill University; Columbia University; WHO
measles live vaccine (IP)
‹#› |
Classe Exemple Données d'inocuité Efficacité chez l'animal Problèmes potentiels Anticorps monoclonaux Zmapp Données historiques sur les Mabs Macaque 100% Disponibilité Antiviral (petite molecule) Favipiravir Enregistré pour la grippe faible Oral : 18-36 comprimés/jour Antiviral (petite molecule) Brincidofovir Phase III pour CMV In vitro Données chez l'animal Antiviral (ARN) siRNA Phase I administration unique Macaque 100% Disponibilité Stinulateur le la réponse immunitaire Interféron Enregistré pour les hépatites Faible Fièvre Contrôle de l'hémorrhagie FX06 Phase II en cardiologie Théorique Pas de données
‹#› |
‹#› |
Merck Vaccines/NewLink Pharmaceuticals/Public Health Agency of Canada
800 flacons donnés à l'OMS par le gouvernement du Canada en août 2014
GSK/NIAID
Les deux vaccins les plus avancés sur le plan de l'évaluation clinique
Kanapathipillai R et al. N Engl J Med 2014. DOI: 10.1056/NEJMp1412166
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
Institut Pasteur, ENS, Aix Marseille University, Ruprecht-Karls University Heidelberg, University Amsterdam, University Utrecht, UCAD, Public Health England
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
Inserm: ITMO Santé Publique - Pôle Recherche Clinique, Claire Levy-Marchal
Denis Malvy (Head of Infectious diseases department, Bordeaux Univ Hospital & Inserm unit 897, Bordeaux) Sakoba Keita (Guinea's national coordinator for the fight against Ebola, Ministry of health, Conakry)
Xavier Anglaret (Programme PACCI/site ANRS, Abidjan, Côte d’Ivoire & Inserm unit 897, Bordeaux) France Mentré (Inserm unit 1137, IAME & CM Nord REACTing, Paris )
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
Efficacy of favipiravir correlates negatively with time since first symptoms Favipiravir for EVD should be given at higher doses than that previously tested in studies in human with influenza
humans with EVD
Evolution of EBOV plasma RNA and infectious loads under treatment; Tolerance of favipiravir; Viral micro-diversity of EBOV; Trough concentrations of favipiravir; Factors associated with mortality , cure at Day 30, toxicity
To ensure that the trial is culturally sensitive, gender-aware and reflexive
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
December 2014: MSF EVD care center in Gueckedou January 2015: French Red Cross EVD care center in Macenta and ALIMA EVD care center in Nzerekore
Age >1 year EVD confirmed by a positive qualitative PCR test Informed consent
Pregnancy (emergency use) Inability to take the drug (encephalopathy; severe vomiting)
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
Evolution of EBOV plasma RNA and infectious loads Grade 3-4 adverse events Viral micro-diversity of EBOV (including resistance mutations) Trough concentrations of favipiravir Cure at Day 30
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
Dr Mounié Barry; CHU Donka-Ministry of Health, Guinea Pr Eric Delaporte; IRD-Inserm, France
virology) and social outcomes of Ebola Virus Disease (EVD)
Multidisciplinary, multicentric prospective observational cohort study of adults and children who recovered from EVD. Three hundred patients followed 18 months
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
PROPHYLACTIC AND THERAPEUTIC EBOLA VACCINES
Pr Yves Lévy; VRI/inserm/Upec, Créteil, France Dr Hervé Raoul, BSL - 4 Inserm Mérieux, France
targeting dendritic cells (DC) and fused to Ebola antigen (Ag), in order to favor activation of antiviral specific immune responses
Evaluation of immune responses and protection conferred by the DC-based vaccine candidates in non-human primates Test therapeutic vaccination with anti-DC Ebol rAbs in combination with antiviral T-705 prophylaxis Phase I/II safety and immunogenicity study in healthy volunteers Elicitation of Ig-specific responses following Immunization of healthy volunteers with anti-DC Ebol rAbs
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
based on Ad26.ZEBOV and MVA-BN-Filo
Coordinator of EBOVAC-2 project in Topic 1 (Phase II trials) Partner of EBOVAC-1 project in Topic 1 (Phase 1 & 3 trials) Partner in Topic 5 (Rapid diagnosis)
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
African countries of a two component prime-boost vaccine for prophylaxis against Ebola: Ad26.ZEBOV prime + MVA-BN-Filo boost
Ad26.ZEBOV: monovalent Ad26 vaccine expressing Mayinga Ebola GP MVA-BN-Filo: multivalent MVA with ZEBOV, SEBOV, Marburg GP and Tai Forest nucleoprotein insert GP of the current strain circulating in West Africa shares 97% homology with ZEBOV GP used in this strategy Complete protection in macaques study with trivalent Ad26 mixture prime (ZEBOV, SEBOV, Marburg) and MVA-BN-Filo boost and Ebola Zaire Kikwit challenge
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
trajectories of patients with suspected Ebola infection in France
for the detection of Ebola virus in blood or urine (CEA & BioFire).
preventive vaccine derived from measles live vaccine
Development and evaluation of the efficacy of hyperimmunes Igs. Identification of new molecules and vaccines based on different approaches including lentiviral vector (Institut Pasteur).
‹#› |
Site Nombre Début du recrutement Fin du recrutement Résultats prelim.
VRC – USA (Bivalent) 20 2 Septembre 2014 Octobre Publié NEJM Nov 2014 Oxford – UK 60 17 Septembre 2014 Novembre Publié NEJM Fev 2015 CVD – Mali 91 8 Octobre 2014 Décembre Jan 2015 Lausanne, Suisse 120 31 Octobre 2014 Décembre Jan 2015
Maryland, USA 20 31 Octobre 2014 Deéembre Jan 2015
‹#› |
Site Nom bre Début Fin du recrutement Résultats prelim.
WRAIR – USA 30 17 Octobre 2014 Déc 2014 Déc 2014 NIAID – USA 30 24 Octobre 2014 Déc 2014 Déc 2014 Genève Suisse 100 10 Nov 2014 Jan 2015 Jan 2015 Allemagne 30 17 Nov 2014 Jan 2015 Jan 2015 Gabon 60 21 Nov 2014 Jan 2015 Jan 2015 Kenya 40 Déc 2014 Jan 2015 Fév 2015 Canada 30 Déc 2014 Dec 2014 Jan 2015 Total volontaires vaccinés Phase I = 320
‹#› |
‹#› |
‹#› |
‹#› |
Stepped Wedge Design for Sierra Leone
A10 March 2015
53 |
Initiation of Phase 1 trials for the two most advanced vaccines
Sept - Oct 2014 2nd Q 2015 Nov-Dec 2014
Agreed protocols (including Phase 3) trials across sites Preparation started of sites for Phase 3 studies in Ebola affected countries Initial safety and immunogenicity from most Phase 1 trials available Start of Phase 3 trials in Ebola affected countries
Jan-Feb 2015
Start of Phase 2 trials Preliminary results vaccine efficacy available
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
February 2015
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
IBEID HIDDEN
CI C
56
Cameroon, Burkina Faso, Côte d’Ivoire, Senegal
Cambodia, Vietnam
Human and Social Science JIKI Trial Cohort of Survivors EBOVAC 2
Sites Extra Sites North Partners
58
Basse Guinée +++
Semaine 3-5 à Conakry = 69% Décès communautaires
Guinée forestière
59
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
In the 3 main countries impacted by Ebola (Guinea, Sierra Leone and Liberia), the epidemic becomes more volatile with spreading sources of infection, but the epidemic has been contained in the epicenters The population is reluctant to visit Ebola care units to get treated
WHAT IS AT STAKE FOR 2015?
The response must be in line with the evolution of the epidemic and must get more mobile with the set up of local teams in charge of ringing the bell and delivering quick solutions Make sure that Ebola Care units will be able to react promptly in case of a new
New treatments have been tested during the epidemic : Favipiravir in Humans and Primates.
WHAT IS AT STAKE FOR 2015?
Access to tested treatments (Favipiravir alone or in combination) must be guaranteed in care units to get them more attractive to patients. Support of the phase 4 of cohort of patients treated with Favipiravir in TCU according to scientific protocols
CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD ARIIS EFS INERIS INSTITUT CURIE INSTITUT MINES-TELECOM UNICANCER IRBA IRSN CIRAD FONDATION MERIEUX
Launching the rebuilding of the health systems affected by the Ebola
Improving the supervision with the set-up of an epidemiological network and warning system
Building capacities in public health
expertise
condition of capacity building
detection of emerging pathogens (Pasteur Institute in Guinea…)
Lamballerie, les chercheurs guinéens, C Lévy-Marchal, B Murgue, Y Yazdanpanah.